Mechanobiology and Resolution of Lung Fibrosis

Pulmonary fibrosis is a devastating and progressive disease marked by replacement of gas-exchanging tissue with collagen-rich scar. The mechanical environment is profoundly altered in pulmonary fibrosis and contributes to disease progression via feedback relationships between cells, the extracellular matrix, and the evolving mechanical environment. Targeting these mechanobiological feedback loops has emerged as a promising approach to interrupt disease progression, though with challenges in how to intervene selectively, safely, and effectively. We posit that further delineation of cell-matrix mechanobiological interactions will be pivotal to promoting fibrosis resolution and should guide efforts to discover and implement new approaches that can preserve or even restore lung function. To set the stage for these advances, we first review the mechanobiology of the healthy lung and the feedback loops that promote fibrosis progression. We then lay out the challenges and opportunities for targeting the fibrotic matrix as an essential element for protecting or restoring lung function.